To date, two mammalian bombesin-like peptides, gastrin-releasing peptide (GRP) and neuromedin B (NMB), have been characterized. These two peptides are widely distributed in mammalian nervous system and GI tract; but, of greatest clinical importance, GRP is expressed by many neoplasms and may stimulate the growth of these neoplasms. Recent studies suggest that there are a number of additional bombesin-like peptides that are yet to be identified and that these peptides likely play an important role in growth and development. Thus, we are attempting to identify new bombesin-like peptides by cross-hybridization with cDNAs encoding previously characterized bombesin-like peptides, as well as by using antibodies to amphibian bombesin-like peptides. Once new bombesin-like peptides are discovered, distribution studies and physiologic studies using the primate model will be established to determine the role of these new peptides in normal and neoplastic processes. To date, we have discovered 3 new amphibian bombesin-like peptides and two new amphibian bombesin receptors. Using low stringency hybridization and various PCR strategies, we are currently searching for their mammalian homologs. By expression in Xenopus oocytes we have begun to define structural requirements of the BRS-3 ligand.